Influenza viruses have on their surfaces two biologically active glycoproteins, a hemagglutinin and a neuraminidase. The object of this proposal is to determine how these two viral components interact with host cells and to thereby elucidate their roles in virus replication. Specifically, we intend to identify and characterize the viral receptors on host cells using a variety of techniques including direct binding studies, the isolation of host cell variants with altered membrane components, and the isolation of the receptors by affinity chromatography. In addition, we will use cells with altered membranes to determine which structral and chemical properties are required for binding the virus to cells. Thus far we have obtained from the surface of susceptible cells glycolipids with terminal galactose residues which prevent binding and which inhibit infectivity of influenza virus. We are in the process of determining the chemical composition of this material and in investigating its mechanism of inhibition. Using labelled inhibitor, we will determine which structural components of the virus bind the inhibitor. We will also compare the membrane components of susceptible cells with those of a cell variant which we have found to be specifically resistant to influenza virus. We will investigate the role of soluble glycoprotein hemagglutination inhibitors in the infectious process and will study their effects on binding of the virus to host cells. The experiments are aimed at acquiring information about mechanisms of virus attachment and penetration which can be of use in controlling the replication of the virus in nature.